Pulsed Radiotherapy for Brain Cancer

Not currently recruiting at 1 trial location

Overseen By Jiayi Huang, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Bevacizumab, Anti-VEGF

Disqualifiers: Leptomeningeal, Metastatic, Radiation necrosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new radiation method called temporally-modulated pulsed radiation therapy (TMPRT) for individuals with IDH-mutant gliomas, a type of brain cancer. The researchers aim to determine if administering radiation in smaller, timed doses can reduce side effects and improve quality of life compared to traditional methods. This trial may suit those whose tumor has recurred after previous brain radiation, provided it has not spread and the prior treatment occurred at least two years ago. As an unphased trial, it offers a unique opportunity to contribute to pioneering research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial requires you to stop taking bevacizumab (a medication used to treat certain types of cancer) at least 4 weeks before starting the study. Other medications like chemotherapy or immunotherapy can be continued, but it's best to discuss with your doctor.

What prior data suggests that this radiation technique is safe for patients with IDH-mutant gliomas?

Research has shown that temporally-modulated pulsed radiation therapy (TMPRT) is generally safe for patients with certain brain tumors. TMPRT delivers radiation in small bursts rather than one large dose. Studies have found it safe and practical for patients who have already received radiation to the brain. Specifically, a study on TMPRT for recurring brain tumors found it to be well-tolerated, with no major safety concerns. This suggests that TMPRT could be a promising treatment option with fewer side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for brain cancer, which often involve continuous radiation, temporally-modulated pulsed radiotherapy (TMPRT) delivers radiation in short, controlled pulses. This unique approach could potentially reduce damage to healthy brain tissue by allowing for recovery periods between radiation pulses. Researchers are excited about TMPRT because it aims to maximize the impact on cancer cells while minimizing side effects, offering a promising new way to improve patient outcomes.

What evidence suggests that TMPRT is effective for brain cancer?

Research has shown that temporally-modulated pulsed radiation therapy (TMPRT) might surpass traditional methods in treating brain cancer. This trial will evaluate TMPRT, which delivers radiation in small, timed doses, potentially killing more tumor cells while sparing healthy cells. The goal is to enhance treatment effectiveness and reduce side effects, easing the patient experience. Early results suggest that TMPRT could better control tumors and lower side effects, potentially improving the quality of life for patients with IDH-mutant gliomas. Although further research is needed, TMPRT appears to be a promising, precise, and effective option for radiation therapy. ^{1 2 3 6 7}

Who Is on the Research Team?

Jiayi Huang, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with IDH-mutant gliomas (brain tumors) who've had prior radiation. They should have a life expectancy of over a year, be able to consent, and women must use birth control. It's not for pregnant individuals or those with certain medical conditions that conflict with the treatment.

Inclusion Criteria

I had targeted radiation to the same area before, but the total dose was under 75 Gy and it was over 6 months ago.

I am using or willing to use birth control during the study.

I had external beam radiation therapy over 2 years ago.

Exclusion Criteria

You are currently pregnant.

I am not using bevacizumab or similar drugs for my treatment.

My cancer has spread to the lining of my brain or other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive temporally-modulated pulsed radiation therapy (TMPRT) daily as 10 pulses of 0.2 Gy each with a 3-minute interval between pulses to a total dose of 54 Gy at 2 Gy per day. Treatment continues for a total of 27 fractions.

6 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of quality of life and symptom burden.

12 months

Assessments at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• TMPRT

Trial Overview The study tests TMPRT, a type of radiotherapy given in small doses at set intervals to potentially increase effectiveness and reduce side effects compared to one large dose. The focus is on patients who've previously received brain radiation therapy.

How Is the Trial Designed?

Group I: Arm 1: temporally-modulated pulsed radiotherapy (TMPRT) Experimental Treatment 1 Intervention

Patients receive TMPRT daily as 10 pulses of 0.2 Gy each with a 3-minute interval between pulses (effective dose rate = 0.0667 Gy/min) to a total dose of 54 Gy at 2 Gy per day. Treatment continues for a total of 27 fractions in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a study of 24 high-grade glioma patients, significant volumetric changes in the tumor bed were observed between immediate postoperative MRI and MRI taken before radiation therapy, leading to a decrease in the volume of brain tissue treated with 46 Gy of radiation.

Using delayed MRI for radiation treatment planning can reduce the volume of healthy brain tissue exposed to radiation, potentially minimizing side effects, while still maintaining effective local control of the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating changes in radiation treatment volumes from post-operative to same-day planning MRI in High-grade gliomas. Champ, CE., Siglin, J., Mishra, MV., et al.[2021]

In a study of 9 patients with brain metastases from lung adenocarcinoma, the combination of intensity-modulated radiation therapy (IMRT) and temozolomide (TMZ) resulted in a high objective response rate of 77.8%, with one complete response and six partial responses, confirming the efficacy of this treatment approach.

Patients receiving the combination treatment experienced fewer severe adverse effects compared to those who only received IMRT, with no grade ≥3 hematologic toxicities reported, and an improvement in quality of life was noted, indicating that the addition of TMZ is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. Li, J., Chai, X., Cao, Y., et al.[2020]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

In a study using a head and neck cancer model with 30 mice, low-dose pulsed radiation treatment (PRT) combined with cisplatin (CDDP) significantly delayed tumor growth more than standard radiation therapy (SRT) combined with CDDP, with PRT achieving an average growth delay of 80.2 days compared to 62.3 days for SRT.

PRT also preserved the tumor's vascular network better than SRT, as indicated by differences in tumor vessel density, which may contribute to its enhanced efficacy in combination with CDDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed Radiation Therapy With Concurrent Cisplatin Results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model. Meyer, K., Krueger, SA., Kane, JL., et al.[2022]

In a study of 87 newly diagnosed glioblastoma patients, only 5% experienced severe myelotoxicity during treatment with temozolomide (TMZ) and radiation therapy, indicating that while the risk exists, it is relatively low.

Factors such as female sex, low pretreatment platelet counts, and specific genetic markers were identified as potential predictors of severe myelotoxicity, suggesting that personalized treatment approaches could help mitigate risks in vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. Lombardi, G., Rumiato, E., Bertorelle, R., et al.[2018]

In a study of 260 patients treated for brain and skull base tumors with photon and particle therapies, no unexpected severe toxicities were reported, indicating a favorable safety profile for these treatments.

The use of particle therapy, particularly protons and carbon ions, shows promise in potentially reducing the risk of secondary malignancies and improving neurocognitive outcomes, although longer follow-up is needed to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. Combs, SE., Kessel, K., Habermehl, D., et al.[2016]

Low-dose pulsed radiation therapy (PRT) and standard radiation therapy (SRT) both effectively delayed tumor growth in head and neck squamous cell carcinoma xenografts, indicating that PRT can be a viable alternative to SRT.

PRT resulted in lower levels of tumor hypoxia compared to SRT in radiosensitive UT-SCC-14 tumors, suggesting that PRT may improve treatment outcomes by reducing hypoxic conditions that can limit the effectiveness of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Pulsed Radiation Therapy on Tumor Oxygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma. Wobb, J., Krueger, SA., Kane, JL., et al.[2022]

In a prospective study of 20 patients with newly diagnosed glioblastoma, pulsed radiation therapy (PRT) combined with temozolomide showed promising effectiveness, with a median overall survival of 20.9 months, which is significantly longer than the 14 months observed in a matched cohort receiving standard radiotherapy.

PRT treatment maintained neurocognitive function and quality of life over the 21-month follow-up period, indicating that this therapy is not only effective but also safe for patients' cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma. Almahariq, MF., Quinn, TJ., Arden, JD., et al.[2021]

Pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) significantly delayed tumor growth in a murine model of radioresistant glioblastoma multiforme (GBM), showing superior efficacy compared to standard radiation therapy with TMZ.

PLRT+TMZ resulted in less damage to normal brain tissue and increased vascularization, suggesting it may be a safer and more effective treatment option for GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed versus conventional radiation therapy in combination with temozolomide in a murine orthotopic model of glioblastoma multiforme. Lee, DY., Chunta, JL., Park, SS., et al.[2022]

A shortened course of radiotherapy (51 Gy in 17 fractions) for malignant glioma patients showed similar survival outcomes to more aggressive treatments, with median survival times ranging from 5 to 68 months based on prognostic groupings.

The treatment was associated with low toxicity and acceptable acute side effects, making it a viable option for patients in poorer prognostic groups (RTOG groups 4-6), but not recommended for those with better long-term survival prospects (RTOG groups 1-3) due to a lack of long-term neurocognitive data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short course radiotherapy is an appropriate option for most malignant glioma patients. Kleinberg, L., Slick, T., Enger, C., et al.[2019]

Proton therapy (PT) offers a promising alternative to traditional photon-based radiotherapy for glioblastoma multiforme (GBM) patients by potentially reducing off-target irradiation and associated toxicities, which is crucial given the aggressive nature of this tumor.

Current research suggests that PT may enhance treatment outcomes for glioma patients, particularly in terms of cognitive sparing and the feasibility of high-rate 'FLASH' radiotherapy, highlighting the need for ongoing clinical trials to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for glioma and glioblastoma. Goff, KM., Zheng, C., Alonso-Basanta, M.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05393258

Temporally-modulated Pulsed Radiation Therapy (TMPRT) ... This clinical trial studies the side effects of temporally-modulated pulsed radiation therapy (TMPRT) in patients with IDH-mutant gliomas who have ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0360301624013270

A Pilot Study of Temporally-Modulated Pulsed Radiation ... This prospective trial aims to assess the safety and quality of life (QOL) impact of TMPRT in recurrent IDHmt gliomas.

3. nature.com nature.com/articles/s41598-024-78370-x

Initial feasibility cohort of temporally modulated pulsed ... Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10290511/

Temporally modulated pulsed proton re-irradiation (TMPPR ... This proton therapy (PT) technique has the radiobiological property to allow an enhanced tumor cell death and an increased normal cell sublethal repair.

5. redjournal.org redjournal.org/article/S0360-3016(24)01327-0/pdf

e252 Poster Q&A Sessions Temporally modulated pulsed radiation therapy (TMPRT) is a novel technique ... treatment for more precise and effective radiation therapy in palliative care.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39496803/

Initial feasibility cohort of temporally modulated pulsed ... We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-05018

Temporally-Modulated Pulsed Radiation Therapy after ... This clinical trial tests the safety and side effects of temporally-modulated pulsed radiation therapy (TMPRT) in treating patients with gliomas.